No abstract

A new effective method for the construction of nitrogen heterocycles incorporating endocyclic pharmacophore sulfonamide fragment, based on the use of easy accessible N-(chlorosulfonyl)imidoyl chloride, CCl3C(Cl)=NSO2Cl (1), has been developed. Thus, a reaction of 1 as bielectrophilic 1,3-C–N–S reagent with benzylamines that act as 1,4-N–C–C-C binucleophiles, affords respective 1,2,4-benzothiadiazepine-1,1-dioxides. On the other hand, 1 reacts with alkenyl amines with the formation of respective N-alkenyl amidines undergoing Lewis acids initiated intramolecular cyclization to afford derivatives of 1,2,4-thiadiazines and 1,2,4-thiadiazocines bearing a halomethyl group able for further functionalization. The first examples of electrophilic heterocyclization of the chlorosulfonyl group onto an alkenyl or alkynyl group have been revealed.

Похідні 2-тіоксотіазолідин-4-ону (роданіну) широко вивчаються, оскільки їм притаманна антибактеріальна, антивірусна, антиракова, протидіабетична і протизапальна активність [1]. Біологічну дію похідних роданінів пов'язують з їх здатністю інгібувати активність серин-треонінових протеїнкіназ родини Pim [2], протеїндисульфідізомерази [3], топоізомерази ІІ [4], карбоангідрази і ацетилхолінестерази [5] та деяких інших протеїнів [6]. Недавно було показано, що тіазоловмісні похідні N-заміщених роданінів здатні ефективно інгібува ти пухлини різних ліній [7].

Synthetic 6-substituted purine derivatives are known to exhibit diverse bioactivity. In this paper, a series of N-(9H-purin-6-yl)-1,2-oxazole-3-carboxamide derivatives were synthesized and evaluated in vitro against xanthine oxidase, an enzyme of purine catabolism. The introduction of aryl substituent at position 5 of the oxazole ring was found to increase the inhibition efficiency. Some of the inhibitors containing 5-substituted isoxazole and purine moieties were characterized by IC50 values in the nanomolar range. According to the kinetic data, the most active N-(9H-purin-6-yl)-5-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,2-oxazole-3-carboxamide demonstrated a competitive type of inhibition with respect to the enzyme-substrate. Molecular docking was carried out to elucidate the mechanism of enzyme-inhibitor complex formation. The data obtained indicate that xanthine oxidase may be one of the possible targets for the bioactive purine carboxamides.